Exploring white matter microstructure and the impact of antipsychotics in adolescent-onset psychosis

Abstract

White matter abnormalities are well-established in adult patients with psychosis. Less is known about abnormalities in the rarely occurring adolescent early onset psychosis (EOP). In particular, whether antipsychotic medication might impact white matter microstructure is not known. Using 3T diffusion weighted imaging, we investigated differences in white matter microstructure and the impact of antipsychotic medication status in medicated (n = 11) and unmedicated (n = 11) EOP patients relative to healthy controls (n = 33), aged between 12-18 years. Using Tract-based Spatial Statistics, we calculate case-control differences in scalar diffusion measures, i.e. fractional anisotropy (FA), axial diffusion (AD) and radial diffusion (RD), and investigated their association with antipsychotic medication in patients. We found significantly lower FA in the left genu of the corpus callosum, the left anterior corona radiata (ACR) and the right superior longitudinal fasciculus in EOP patients relative to healthy controls. AD values were also lower in the left ACR, largely overlapping with the FA findings. Mean FA in the left ACR was significantly associated with antipsychotic medication status (Cohen's d = 1.37, 95% CI [0.01, 2.68], p = 0.008), showing higher FA values in medicated compared to unmedicated EOP patients. The present study is the first to link antipsychotic medication status to altered regional FA in the left ACR, a region hypothesized to contribute to the etiology of psychosis. Replications are warranted to draw firm conclusions about putatively enhancing effects of antipsychotic medication on white matter microstructure in adolescent-onset psychosis.

Fig 1. Lower Fractional Anisotropy (FA) in Early Onset Psychosis (EOP) patients in comparison to healthy controls.

Displayed are significant FWE-corrected TBSS results (red-yellow, p ≤ 0.01), contrasting EOP patients against healthy controls, overlaid on the study-specific mean FA skeleton in green and the mean FA image. Results shown underwent threshold-free cluster enhancement and were corrected for age and sex. CC = corpus callosum, ACR = anterior corona radiata, SLF = superior longitudinal fasciculus, R = right, L = left.

Fig 2. Extracted scalar diffusion values of the left anterior corona radiata (ACR) cluster stratified by antipsychotic use, in comparison to the healthy controls (HC).

As scalar diffusion measures largely vary in their value ranges, the extracted mean values were z-standardized using the following formula: z = (participant’s value–group mean) / standard deviation. Data is z-standardized and presented as boxplots for the different scalar diffusion measures overlaid with raw data points. HC are depicted in white, EOP patients on antipsychotic medication in dark grey and EOP patients off antipsychotic medication in light grey. EOP = Early onset psychosis, AP = Antipsychotic use (on = yes, off = no), AD = axial diffusion, FA = fractional anisotropy, RD = radial diffusion. Significant differences in scalar measures between patient subgroups, based on linear regression models, are indicated with a star.